Oral tolerance in the absence of naturally occurring Tregs

作者：Daniel Mucida · 发表于：Journal of Clinical Investigation · 年份：2005 · DOI：10.1172/jci24487 · 被引用次数：495 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Asthma and respiratory diseases

Mucosal tolerance prevents pathological reactions against environmental and food antigens, and its failure results in exacerbated inflammation typical of allergies and asthma.One of the proposed mechanisms of oral tolerance is the induction of Tregs.Using a mouse model of hyper-IgE and asthma, we found that oral tolerance could be effectively induced in the absence of naturally occurring thymus-derived Tregs.Oral antigen administration prior to i.p. immunization prevented effector/memory Th2 cell development, germinal center formation, class switching to IgE, and lung inflammation.Oral exposure to antigen induced development of antigen-specific CD4 + CD25 + Foxp3 + CD45RB low cells that were anergic and displayed suppressive activity in vivo and in vitro.Oral tolerance to the Th2 allergic response was in large part dependent on TGF-β and independent of IL-10.Interestingly, Tregs were also induced by single i.p. immunization with antigen and adjuvant.However, unlike oral administration of antigen, which induced Tregs but not effector T cells, i.p. immunization led to the simultaneous induction of Tregs and effector Th2 cells displaying the same antigen specificity.Nonstandard abbreviations used: BAL, bronchoalveolar lavage; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; GITR, glucocorticoid-induced TNF receptor; GC, germinal center; Imm, mice given OVA-HA i.p. immunization; mLN, mesenteric lymph node; Oral, mice fed OVA in drinking water; RAG, recombination activating ge...